Complex organisms such as vertebrates and insects have developed specialized chemosensory organs in order to locate food, evaluate mates, and avoid toxins. The sensing of volatile odors is particularly challenging because odors are often present at low levels in turbulent plumes, yet many animal behaviors rely on the faithful coding of odor signals by olfactory receptor neurons. The past few decades have witnessed an explosion of research into olfactory systems, following the cloning of the first odor receptors. Initial research focused on understanding odor receptor function, characterizing their odor response profiles, and understanding their effects on behavior. However, many open questions remain regarding the molecular and cellular mechanisms supporting olfaction in the periphery, particularly in regards to insect olfaction. What signaling mechanisms are downstream of insect odor receptor activation? How are odors removed from the peri-neuronal space? What contribution do non- neuronal support cells make to olfactory neuron activity? How are the support cells of olfactory sensilla similar or different than those in sensilla that mediate other sensory modalities? My lab seeks answers for these questions in the Drosophila antenna, their primary olfactory organ. This versatile model organism is advantageous for such studies because we can exploit the large number of available genetic tools and existing knowledge on its stereotyped receptor and neuronal organization. Here we propose to study the functions of several candidate genes that have arisen from our recent computational screen, and may provide answers to several outstanding questions in field olfaction field as described above. One project centers on several highly conserved antennal-enriched signaling genes and their putative roles in amplification and desensitization downstream of odor receptor activation. Two additional projects focus on the interactions between non-neuronal support cells and the signaling of olfactory neurons. One investigates the role of support cells in odor degradation using candidate metabolic genes that arose from our screen and an RNASeq-based method to identify new candidates. We will also elucidate the potential differences in function between the major support cell classes, which are found not only in olfactory sensilla but also in sensilla that mediate other physiological functions.